Scavenger supports and the use thereof in a process for the extraction of metals

ABSTRACT

There is provided a process for removing metal from solution wherein a solution comprising a metal is contacted with a scavenger support, whereby the scavenger support binds to at least some of the metal in solution thereby decreasing the amount of metal in solution, characterized in that the scavenger support comprises a functionalized support comprising pendant groups selected from 1,3-ketoesters or 1,3-ketoamides or mixtures thereof attached to a support wherein a number of the pendant groups are reacted with an amine. Scavenger supports comprising a functionalized support comprising pendant 1,3-ketoester or 1,3-ketoamide groups of formula 1: wherein R 1  is an optionally substituted hydrocarbyl, perhalogenated hydrocarbyl or heterocyclyl group; X is O or NR 2 , wherein the free valence of O or NR 2  is bonded to a support optionally via a linker; and R 2  is hydrogen, an optionally substituted hydrocarbyl, or heterocyclyl group, wherein a number of the pendant groups are reacted with an amine are also provided. Preferred scavenger supports include scavenger supports comprising pendant 3-iminoesters, 3-iminoamides, 2,3-enaminoesters or 2,3-enaminoamides pendant groups of Formula (3) or (4): wherein R 1  is an optionally substituted hydrocarbyl, perhalogenated hydrocarbyl or heterocyclyl group; X is O or NR 2 , wherein the free valence of O or NR 2  is bonded to a support optionally via a linker; R 2  is hydrogen, an optionally substituted hydrocarbyl, or heterocyclyl group; R 4  is a substituent group; and R 5  is hydrogen or a substituent group, or R 4  and R 5  may optionally be linked in such a way so as to form an optionally substituted heterocyclic ring, or tautomers or salts thereof.

This invention relates to scavenger supports and to processes for theremoval of metal values especially palladium from solution usingscavenger supports, particularly scavenger supports obtainable byreacting ketoester resin supports with amines.

Over the past few years, the exploration and utilization ofcombinatorial chemistry (and multi parallel synthesis) as apharmaceutical drug discovery technology has rapidly evolved. The fieldof combinatorial/multi parallel chemistry has expanded to include notonly solid and solution-phase methods for expedited compound synthesis,but also hybrid approaches which combine the purification advantages ofsolid-phase synthesis with the flexibility of solution-phase synthesis.(Kaldor, S. W. and Siegel, M. G., Curr. Opin. Chem. Biol. 1997, 1,101-106 and Thompson, L. A. and Ellman J. A., Chem. Rev. 1996, 96,555-600) Inherent in any approach to produce chemical libraries is theneed to rapidly purify, isolate, and manipulate chemical library membersduring their preparation.

Polymeric scavenging reagents have emerged as useful tools forcombinatorial synthesis, particularly, for solution-phase chemicallibrary synthesis. These materials are employed to remove, or scavenge,unwanted reagents or bi-products and thus aid in the purification ofmaterials. (Creswell, M. W. et. al., Tetrahedron, 1998, 54, 3983-3998;Kaldor, S. W. et. al., Tetrahedron Lett. 1996, 37, 7193-7196; Flynn, D.L. et. al., S., J. Am. Chem. Soc. 1997, 119, 4874-4882; Kaldor, S. W.et. al., Bioorg. Med. Chem. Lett. 1996, 24(6), 3041-3044; Caldarelli, M.et. al., J. Chem. Soc., Perkin Trans. 1. 1999, 107-110; Booth, R. J. andHodges, J. C., J. Am. Chem. Soc. 1997, 119, 4882-4886; Gayo, L. M. andSuto, M. J., Tetrahedron Lett. 1997, 38, 513-516; and Siegel, M. G. et.al., Tetrahedron Lett. 1997, 38, 3357-3360). Typically, the polymericscavengers are added after the chemical reaction is complete to removeexcess reactants and bi-products. The resulting resin bound reactantsare removed by simple filtration leaving the product in solution.Examples of polymeric scavenger reagents include:

All the above resins are made by initial synthesis of a polystyrene orpolystyrene copolymer bead followed by one or more chemical modificationsteps to introduce the scavenging functionality. For example, theisocyanate functional bead which is sold as a scavenger for amines canbe prepared from the Merrified resin via the amino methyl polystyrene:

The resins used are typically lightly crosslinked polystyrenes (1 to 3%divinyl benzene) which typically require solvents that will swell theresin to allow reagents to access the polymer bound functional groups.Alternatively the resin could be a macroporous resin (highdivinylbenzene content) which has permanent porosity allowing reactantsto access the functional groups independent of the solvent type.

Many of the scavenger supports that are employed in combinatorialapplication are designed for the removal of organic reagents. One areaof synthesis where the use of scavenger supports is potentially usefulis for example in metal mediated reactions. Metal mediated reactions areuseful in synthesis for performing a variety of chemicaltransformations, however typically the catalysts employed in thesereactions are transition metal derived.

Additionally the removal of catalyst residues from metal-catalysedprocesses at the industrial scale is becoming more important. Stricterregulations on the contamination of products and wastestreams havegenerated a higher need for alternative methods of removing heavy metalsfrom these products and wastestreams. In particular in thepharmaceutical industry regulation by the Federal Drug Administration(FDA) has resulted in very low target levels of transition metals inActive Pharmaceutical Ingredients (APIs). Additionally metalcontamination in a pharmaceutical intermediate can interfere withchemistry carried out at a later stage in the manufacturing process.

There is therefore a need for functionalised supports which act asscavengers for metals, especially transition metals, and which show goodchemical stability.

According to a first aspect of the present invention there is provided aprocess for removing metal from solution wherein a solution comprising ametal is contacted with a scavenger support, whereby the scavengersupport binds to at least some of the metal in solution therebydecreasing the amount of metal in solution, characterised in that thescavenger support comprises a functionalised support comprising pendantgroups selected from 1,3-ketoesters or 1,3-ketoamides or mixturesthereof attached to a support wherein a number of the pendant groups arereacted with an amine.

In the process of the present invention, the choice of amine mayinfluence the affinity and/or selectivity of the scavenger support tobind metals.

Typically, the metal is a transition metal. Preferably, the metal is aplatinum group metal (Group 8, 9 or 10), and more preferably the metalis palladium. Preferably, the metal is present in solution as a metalsalt, a metal complex or a complexed metal salt. Preferred metal saltsinclude metal salts of carboxylic acids, for example metal acetates,metal halides, metal chlorides and bromides, and metal salts ofacetoacetates. Preferred complexed metal salt include metal-ligandhalides wherein the ligand is one or more phosphines, for exampletriphenylphosphine, one or more amines, for example triethylamine, orone or more nitrites, for example acetonitrile, or mixtures thereof.Examples of metal salts, metal complexes or complexed metal saltsinclude Pd(OAc)₂, Tris(dibenzylideneacetone)dipalladium(0), PdCl₂,CoCl₂(PPh₃)₂, Ni(Acac)₂, NiCl₂(PPh₃)₂, OV(Acac)₂, [Rh(OAc)₂]₂, andCu(Acac)₂.

In some cases, the exact nature of the metal species is not know as itis derived from a catalyst species used during a metal catalysedreaction, which may have been changed by the reaction conditions or theprocessing conditions after the reaction, for example by exposure toheat, pressure, reagents, solvents, processing aids, extractionprocesses, filtration and other such processes typically carried outduring chemical processing. In some cases, the metal species may bepresent as a result of contamination during processing, for example byuse of inappropriate processing materials or processing conditions (suchas use of hydrochloric acid in stainless steel vessels), resulting incontamination of the desired product from undesired metal residues. Ingeneral where the nature of the metal species is not known the presenceof the metal is detected by the use of appropriate analytical methods,such as Inductively Coupled Plasma or Atomic Absorption Spectrometry.

In the process of the present invention, the functonalised support mayfirst be reacted with an amine to give the scavenger support, then thescavenger support may be added to a solution comprising a metal. Thescavenger support loaded with metal is then separated from the solution,preferably by filtration, the contact time being such as to allow for atleast partial depletion of the metal in solution. Alternatively, asolution comprising a metal is passed through a mass or column ofscavenger support, the dwell time being such as to allow for at leastpartial depletion of the metal in solution. Contact or dwell time can bedetermined by monitoring reductions in levels of metal in solution.

The process of the present invention may be carried out in the presenceof a solvent. Suitable solvents include any solvent which is compatiblewith the scavenger support. Suitable solvents include solvents capableof swelling scavenger supports based on crosslinked resins or solventcapable of entering the pores of scavenger supports based on macroporousresins. Suitable solvents may be selected from polar, non-polar, proticand aprotic solvents. Examples of suitable solvents include aliphatichydrocarbons such as hexane and heptane, aromatic hydrocarbons such astoluene and xylene, chlorinated hydrocarbons such as dichloromethane(DCM), and chloroform, ethers such as diethyl ether, methyl-tert-butylether and tetrahydrofuran (THF), esters such as ethyl acetate andisopropyl acetate, ketones such as acetone and methyl ethyl ketone,dipolar aprotic solvents such as N,N-dimethylformamide (DMF),dimethylsulphoxide (DMSO) and N-methylpyrrolidinone (NMP), nitriles suchas acetonitrile and propionitrile, alcohols such as methanol andpropan-2-ol, and water and mixtures thereof. Preferred solvents includetoluene, THF, DCM, DMF and propan-2-ol.

The process of the present invention may be applied to removing themetals from mixtures resulting from a chemical reaction. A chemicalreaction mixture may comprise a large variety of components, including,but not being limited to, starting materials, solvents, reagents,catalysts, by-products and products. The mixture from such a chemicalreaction may be contacted directly with the scavenger support of thepresent invention whereby the scavenger support binds to at least someof the metal in solution thereby decreasing the amount of metal insolution. The process of the present invention may be used as part of alarger process to isolate and purify the desired product from thereaction mixture. Thus, the process of the present invention may be usedas a first, intermediate or last step in removing the unwantedcomponents of the mixture, such as starting materials, solvents,reagents, catalysts and by-products. The process of the presentinvention may be used in combination or concurrently with otherpurification processes. Such purification processes are well known to aperson skilled in the art. Particularly the process of the presentinvention may be used concurrently with other solid-phase purificationmethods, such as scavenging for acids, bases, nucleophiles,electrophiles or other specific components, solid phase extraction(SPE), chromatography, clarification. When used concurrently, theprocess of the present invention may lead to low levels of metal in theproduct with no extra processing steps.

The process of the present invention may be carried out at temperaturesranging from −100 to 250° C., preferably from −10 to 100° C., morepreferably from 10 to 40° C. and most preferably at ambient temperature,for example from 15 to 30° C.

In the process of the present invention preferably sufficient scavengersupport is employed to effect the removal of substantially all themetal. Preferably, the ratio of scavenger support to metal solutionemployed is directly related to the concentration of metal present andthe percentage of active functionality on the scavenger support. Thepercentage active functionality on the scavenger support represents thepercentage 1,3-ketoester and/or 1,3-ketoamide pendant groups of thefunctional support that have been reacted with amine. The ratio of molarconcentration of active functionality on the scavenger support to molarconcentration of metal in solution may be in the range from 1:1 to100:1. Preferably an excess of active functionality is employed, forexample ratios in the range of 1:1 to 20:1 or more preferably in therange of 1:1 to 4:1. Such excesses may promote effective and fastremoval of the metal.

The functional supports comprising pendant 1,3-ketoester or1,3-ketoamide groups which are reacted with amines to give the scavengersupport which is employed in the process of the present invention canhave the 1,3-ketoester or 1,3-ketoamide pendant groups attached directlyto a support or attached to a support through a linking group.Preferably, the 1,3-ketoester or 1,3-ketoamide pendant groups areattached to a support through a linking group. Suitable linking groupsinclude those groups as set out below in the definition of L.

The functional supports to which the pendant 1,3-ketoester or1,3-ketoamide groups are attached include inorganic and organicsupports. Preferably, the support is an organic support, more preferablyan organic resin support, particularly synthetic organic resins.

The 1,3-ketoester or 1,3-ketoamide pendant groups include groups offormula 1:

wherein

-   -   R¹ is an optionally substituted hydrocarbyl, perhalogenated        hydrocarbyl or heterocyclyl group;    -   X is O or NR², wherein the free valence of O or NR² is bonded to        a support optionally via a linker; and    -   R² is hydrogen, an optionally substituted hydrocarbyl, or        heterocyclyl group.

Hydrocarbyl groups which may be represented by R¹ and R² include alkyl,alkenyl and aryl groups, and any combination thereof, such as aralkyland alkaryl, for example benzyl groups.

Alkyl groups which may be represented by R¹ and R² include linear andbranched alkyl groups comprising up to 20 carbon atoms, particularlyfrom 1 to 7 carbon atoms and preferably from 1 to 5 carbon atoms. Whenthe alkyl groups are branched, the groups often comprise up to 10branched chain carbon atoms, preferably up to 4 branched chain atoms. Incertain embodiments, the alkyl group may be cyclic, commonly comprisingfrom 3 to 10 carbon atoms in the largest ring and optionally featuringone or more bridging rings. Examples of alkyl groups which may berepresented by R¹ and R² include methyl, ethyl, propyl, 2-propyl, butyl,2-butyl, t-butyl and cyclohexyl groups.

Alkenyl groups which may be represented by R¹ and R² include C₂₋₂₀, andpreferably C₂₋₆ alkenyl groups. One or more carbon-carbon double bondsmay be present. The alkenyl group may carry one or more substituents,particularly phenyl substituents. Examples of alkenyl groups includevinyl, styryl and indenyl groups.

Aryl groups which may be represented by R¹ and R² may contain 1 ring or2 or more fused rings which may include cycloalkyl, aryl or heterocyclicrings. Examples of aryl groups which may be represented by R¹ and R²include phenyl, tolyl, fluorophenyl, chlorophenyl, bromophenyl,trifluoromethylphenyl, anisyl, naphthyl and ferrocenyl groups.

Perhalogenated hydrocarbyl groups which may be represented by Rindependently include perhalogenated alkyl and aryl groups, and anycombination thereof, such as aralkyl and alkaryl groups. Examples ofperhalogenated alkyl groups which may be represented by R include —CF₃and —C₂F₅.

Heterocyclic groups which may be represented by R¹ and R² independentlyinclude aromatic, saturated and partially unsaturated ring systems andmay constitute 1 ring or 2 or more fused rings which may includecycloalkyl, aryl or heterocyclic rings. The heterocyclic group willcontain at least one heterocyclic ring, the largest of which willcommonly comprise from 3 to 7 ring atoms in which at least one atom iscarbon and at least one atom is any of N, O, S or P. Examples ofheterocyclic groups which may be represented by R¹ and R² includepyridyl, pyrimidyl, pyrrolyl, thiophenyl, furanyl, indolyl, quinolyl,isoquinolyl, imidazoyl and triazoyl groups.

When any of R¹ or R² is a substituted hydrocarbyl or heterocyclic group,the substituent(s) should be such so as not to adversely affect the rateor selectivity of the reaction. Optional substituents include halogen,cyano, nitro, hydroxy, amino, thiol, acyl, hydrocarbyl, perhalogenatedhydrocarbyl, heterocyclyl, hydrocarbyloxy, mono or di-hydrocarbylamino,hydrocarbylthio, esters, carbonates, amides, sulphonyl and sulphonamidogroups wherein the hydrocarbyl groups are as defined for R¹ and R²above. One or more substituents may be present.

R¹ is preferably an alkyl group, most preferably a methyl group.

R² is preferably hydrogen or an alkyl group. When R² is an alkyl group,preferably R² is a methyl group. Most preferably R² is hydrogen.

Supports include inorganic supports and organic supports, particularlypolymer supports.

Inorganic supports may be derived from naturally occurring inorganicmaterials or matrices or may be synthesised. Inorganic materials ormatrices include glasses, silicas, aluminas, titanates and hybrid oxidesthereof, graphites, oxides and zeolities. Certain inorganic supports maybe derived from the reaction of inorganic materials or matrices withfunctionalising reagents either to give an inorganic support comprisingpendant 1,3-ketoester or 1,3-ketoamide groups or to give a support withsuitable functionalisation, for example pendant halo, hydroxy or aminogroups to which the pendant 1,3-ketoester or 1,3-ketoamide groups can beattached directly or through a linking group.

In certain embodiments, an amino functionalised silica is reacted withdiketene, 2,2,6-trimethyl-4H-1,3-dioxin-4-one or esters of acetoaceticacid such as t-butyl acetoacetate (in an ester-amide exchange reaction)to form a silica support with pendant 1,3-ketoamide groups.

In further embodiments, an amino functionalised silica is reacted with amultifunctional ketoester or ketoamide, examples of which includeethylene glycol diacetoacetate, ethylene bisacetoacetamide,1,1,1-tris(acetoacetoxymethyl)propane, diacetoacet-o-tolidide,diacetoacet-1,4-phenylenediamide,diacetoacet-2,5-dimethyl-1,4-phenylenediamide,diacetoacet-2-chloro-5-methyl-1,4-phenylenediamide anddiacetoacet-2,5-dichloro1,4-phenylenediamide, resulting in the silicabeing attached to pendant ketoester or ketoamide groups via a ketoamidelinkage, as shown below.

Alternatively, silica supports with pendant 1,3-ketoester groups can beobtained by the above methods by using a hydroxy functionalised silica,for example by reacting a hydroxy functionalised silica with diketene,2,2,6-trimethyl-4H-1,3-dioxin-4-one or esters of acetoacetic acid suchas t-butyl acetoacetate (in an transesterification reaction) to form asilica support with pendant 1,3-ketoester groups.

Polymer support may be derived from the polymerisation of a compositioncomprising one or more monomers, and is preferably derived from thepolymerisation a composition comprising of two or more monomers. Themonomers may contain one or more polymerisable double bonds. Preferablythe polymer support is derived from the polymerisation of a compositioncomprising one or more monomers containing only one polymerisable doublebond, and one or more monomers containing two or more polymerisabledouble bonds. Most preferably the polymer support is derived from thepolymerisation of a composition comprising one or two monomerscontaining only one polymerisable double bond, and one monomercontaining two or three polymerisable double bonds.

Examples of monomers containing only one polymerisable double bondinclude styrene and substituted styrenes such as α-methyl styrene,methyl styrene, t-butyl styrene, bromo styrene and acetoxy styrene;alkyl esters of mono-olefinically unsaturated dicarboxylic acids such asdi-n-butyl maleate and di-n-butyl fumarate; vinyl esters of carboxylicacids such as vinyl acetate, vinyl propionate, vinyl laurate and vinylesters of versatic acid such as VeoVa 9 and VeoVa 10 (VeoVa is atrademark of Shell); acrylamides such as methyl acrylamide and ethylacrylamide; methacrylamides such as methyl methacrylamide and ethylmethacrylamide; nitrile monomers such as acrylonitrile andmethacrylonitrile; and esters of acrylic and methacrylic acid,preferably optionally substituted C₁₋₂₀alkyl and C₁₋₂₀cycloalkyl estersof acrylic and methacrylic acid, such as methyl acrylate, ethylacrylate, n-butyl acrylate, 2-ethylhexyl acrylate, i-propyl acrylate,and n-propyl acrylate, methyl methacrylate, ethyl methacrylate, n-butylmethacrylate, 2-ethylhexyl methacrylate, i-propyl methacrylate, n-propylacrylate, hydroxyethyl acrylate, hydroxyethyl methacrylate,N,N-dimethylaminoethyl acrylate and N,N-dimethylaminoethyl methacrylate.Functional derivatives of the foregoing monomers containing only onepolymerisable double bond can also be employed.

Examples of monomers containing two or more polymerisable double bondsinclude divinylbenzene (DVB), trivinylbenzene, and multifunctionalacrylates and methacrylates such as ethylene glycol diacrylate, ethyleneglycol dimethacrylate, trimethylolpropane triacrylate,trimethylolpropane trimethacrylate, ethylene bisacrylamide,pentaerythritol triacrylate, pentaerythritol tetraacrylate,pentaerythritol trimethacrylate, pentaerythritol tetramethacrylate andN,N-bis-acryloyl ethylene diamine.

In certain embodiments, polymer supports are derived from thepolymerisation of monomers selected from styrene and substitutedstyrenes, divinylbenzene, esters of acrylic, esters of methacrylic acid,alkyl esters of mono-olefinically unsaturated dicarboxylic acids, vinylesters of carboxylic acids, acrylamides, methacrylamides and functionalderivatives thereof. Preferred polymer supports are derived form thepolymerisation of monomers selected from styrene and substitutedstyrenes, divinylbenzene, esters of acrylic acid and esters ofmethacrylic acid. Particularly preferred polymer supports are derivedfrom the polymerisation of a mixture of styrene monomers, divinylbenzenemonomers and methacrylate ester monomers, or are derived from thepolymerisation of a mixture of styrene monomers, divinylbenzene monomersand acrylate ester monomers.

When polymer supports are derived from the polymerisation ofcompositions comprising monomers containing two or more polymerisabledouble bonds, the polymer support can exhibit varying degrees ofcrosslinking. The extent of crosslinking in these polymers can beexpressed in percentage terms and corresponds to the number of moles ofpolymerisable double bonds derived from monomers containing two or morepolymerisable double bonds as a percentage of the total number of molesof polymerisable double bonds.

Where the polymer support of the functional support exhibits only lowlevels of crosslinking, such as from 1% to 5%, or commonly from 1% to3%, these crosslinked scavenger supports are routinely contacted withsolvents which cause the scavenger support to swell. Such functionalsupports are frequently referred to as microporous resins.

In many embodiments, the microporous resin is swelled in the solvent ofchoice to allow ready access to the functional groups on the resin.Solvents of choice can be predicted by considering the polymercomposition and are often those solvents which would be “good solvents”for a theoretical linear polymer which may be made from a similarcomposition but with no crosslinking agent present.

Preferred swell ratios for a microporous resin fall in the range of from3 to 20, more preferably 5 to 20. The swell ratio is defined as:—

${{Swell}\mspace{14mu}{Ratio}} = \frac{{Vol}_{final} - {Vol}_{initial}}{{Vol}_{initial}}$

-   -   Vol_(final)=Final volume occupied by resin after allowing the        resin to fully swell in a given solvent.    -   Vol_(initial)=Initial dry bed volume of resin.

Where the polymer support of the functional support exhibits higherlevels of crosslinking, such as from 20% to 90%, or commonly from 30% to80%, these highly crosslinked functional supports often have permanentporosity thus access of reagents to the pendant groups attached to thepolymer support is mainly independent of solvents. Such functionalsupports are frequently referred to as macroporous resins.

The term macroporous indicates a class of resins which have a permanentwell developed porous structure. Importantly, these resins can have muchhigher surface areas (as measured by nitrogen BET) in the dry state thangel type resins. Typically, surface areas in the dry state can rangefrom 50 to 1000 m²/g. Although there is no universally accepteddefinition of a macroporous resin, in the case of styrene-DVB resins ithas been suggested that a macroporous resin may be defined as resinwhich in the dry state when exposured to cyclohexane exhibits acyclohexane uptake of at least 0.1 m² g⁻¹ over 16 h (Millar, J. R. et.al., J. Chem. Soc., 1996, 218).

Macroporous resins are often formed when the composition comprisingmonomers containing two or more polymerisable double bonds ispolymerised in the presence of a porogen. The porogen causes phaseseparation of the polymer matrix. Removal of the porogen and dryingyields rigid, opaque, permanently porous beads. Phase separation iscontrolled by the nature and level of the porogen employed, and thelevel of crosslinking agent employed.

The selection of monomers and/or crosslinking agents from which thefunctional support is derived may in part be dictated by the desiredmorphology of the scavenger support, and the solvent or reaction systemsin which the scavenger supports will be employed. The relationshipsbetween morphology and monomer compositions are reviewed in Sherrington,D. C., J. Chem. Soc., Chem Commun., 1998, 2275, of which the teaching ofpages 2278 to 2284 are incorporated herein by reference.

Where the pendant 1,3-ketoester or 1,3-ketoamide groups are attachedeither directly or by means of a linker to the polymer support, theattachment is made to the repeat units of the polymer support. Where thepolymer support is derived from more than one monomer type, there willbe more than one type of repeat unit. Preferably the 1,3-ketoester or1,3-ketoamide groups are attached either directly or by means of alinker to only one type of repeat unit. Preferably the repeat unit towhich the 1,3-ketoester or 1,3-ketoamide groups are attached eitherdirectly or by means of a linker is derived from a single monomer typewhich is a methacrylate or acrylate derived monomer.

The pendant 1,3-ketoester or 1,3-ketoamide groups which are attachedeither directly or by means of a linker to the polymer support may beintroduced by reaction of a preformed polymer support withfunctionalising reagents, or may be introduced during the polymerisationof the polymer support.

In certain embodiments, an amino functionalised polymer, such as anamino polystyrene, is reacted with diketene,2,2,6-trimethyl-4H-1,3-dioxin-4-one or esters of acetoacetic acid suchas t-butyl acetoacetate (in an ester-amide exchange reaction) to form apolystyrene support with pendant 1,3-ketoamide groups.

In further embodiments, an amino functionalised polymer, such as anamino polystyrene, is reacted with a multifunctional ketoester orketoamide, examples of which include ethylene glycol diacetoacetate,ethylene bisacetoacetamide, 1,1,1-tris(acetoacetoxymethyl)propane,diacetoacet-o-tolidide, diacetoacet-1,4-phenylenediamide,diacetoacet-2,5-dimethyl-1,4-phenylenediamide,diacetoacet-2-chloro-5-methyl-1,4-phenylenediamide anddiacetoacet-2,5-dichloro1,4-phenylenediamide, resulting in the polymerbeing attached to pendant ketoester or ketoamide groups via a ketoamidelinkage, as shown below.

Alternatively, polymer supports with pendant 1,3-ketoester groups can beobtained by the above methods by using a hydroxy functionalised polymer,for example by reacting a hydroxy functionalised polystyrene withdiketene, 2,2,6-trimethyl-4H-1,3-dioxin-4-one or esters of acetoaceticacid such as t-butyl acetoacetate (in an transesterification reaction)to form a polystyrene support with pendant 1,3-ketoester groups.

Preferably, where the pendant 1,3-ketoester or 1,3-ketoamide group areattached by means of a linker to the polymer support, the functionalsupport is derived from the polymerisation of a composition comprising afunctionalised monomer comprising pendant 1,3-ketoester or 1,3-ketoamidegroups attached by means of a linker to a single monomer type. Morepreferably, the functional support is derived from the polymerisation ofa composition comprising two or more monomers, wherein at least onemonomer is a functionalised monomer comprising pendant 1,3-ketoester or1,3-ketoamide groups attached by means of a linker to a single monomertype. Most preferably the functional support is derived from thepolymerisation of a composition comprising one or more monomerscontaining only one polymerisable double bond, one or more monomerscontaining two or more polymerisable double bonds, and a functionalisedmonomer comprising pendant 1,3-ketoester or 1,3-ketoamide groupsattached by means of a linker to a single monomer type. Polymer supportsderived from the polymerisation of a composition comprising one or twomonomers containing only one polymerisable double bond, one monomercontaining two or three polymerisable double bonds and a functionalisedmonomer comprising pendant 1,3-ketoester or 1,3-ketoamide groupsattached by means of a linker to a single monomer type are highlypreferred.

Functional supports may be derived from the polymerisation ofcompositions comprising a functionalised monomer comprising pendant1,3-ketoester or 1,3-ketoamide groups attached by means of a linker to asingle monomer type, and one or more monomers selected from the groupcomprising styrene and substituted styrenes, such as α-methyl styrene,methyl styrene, t-butyl styrene, bromo styrene and acetoxy styrene;alkyl esters of mono-olefinically unsaturated dicarboxylic acids, suchas di-n-butyl maleate and di-n-butyl fumarate; vinyl esters ofcarboxylic acids such as vinyl acetate, vinyl propionate, vinyl laurateand vinyl esters of versatic acid such as VeoVa 9 and VeoVa 10 (VeoVa isa trademark of Shell); acrylamides such as methyl acrylamide and ethylacrylamide; methacrylamides such as methyl methacrylamide and ethylmethacrylamide; nitrile monomers such as acrylonitrile andmethacrylonitrile; esters of acrylic and methacrylic acid, preferablyoptionally substituted C₁₋₂₀alkyl and C₁₋₂₀cycloalkyl esters of acrylicand methacrylic acid, such as methyl acrylate, ethyl acrylate, n-butylacrylate, 2-ethylhexyl acrylate, i-propyl acrylate, and n-propylacrylate, methyl methacrylate, ethyl methacrylate, n-butyl methacrylate,2-ethylhexyl methacrylate, i-propyl methacrylate, n-propyl acrylate,hydroxyethyl acrylate, hydroxyethyl methacrylate, N,N-dimethylaminoethylacrylate and N,N-dimethylaminoethyl methacrylate; divinylbenzene;trivinylbenzene; and multifunctional acrylates and methacrylates such asethylene glycol diacrylate, ethylene glycol dimethacrylate,trimethylolpropane triacrylate, trimethylolpropane trimethacrylate,ethylene bisacrylamide, pentaerythritol triacrylate, pentaerythritoltetraacrylate, pentaerythritol trimethacrylate, pentaerythritoltetramethacrylate and N,N-bis-acryloyl ethylene diamine. The singlemonomer type to which the pendant 1,3-ketoester or 1,3-ketoamide groupsare attached by means of a linker is preferably a methacrylate oracrylate derived monomer unit.

Preferably the functionalised monomer comprising pendant 1,3-ketoesteror 1,3-ketoamide groups has the general formula 2:

wherein

-   -   each X independently is O or NR²;    -   R¹ and R² are as defined herein before above;    -   R³ is H or an optionally substituted hydrocarbyl, perhalogenated        hydrocarbyl or heterocyclyl group; and    -   L is a linking group.

Optionally substituted hydrocarbyl, perhalogenated hydrocarbyl orheterocyclyl groups which may be represented by R³ are as defined for R¹above.

More preferably the functionalised monomer comprising pendant1,3-ketoester or 1,3-ketoamide groups has the general formula 2a:

wherein

-   -   X is O or NR²;    -   R¹ and R² are as defined herein before above;    -   R³ is H or an optionally substituted hydrocarbyl, perhalogenated        hydrocarbyl or heterocyclyl group; and    -   L is a linking group.

Linking groups which may be represented by L include optionallysubstituted methylene, polymethylene, ether, polyether or cyclicbridging units.

Methylene and polymethylene bridging units which may be represented by Linclude linear and branched alkylene chains comprising up to 20 carbonatoms, particularly from 1 to 7 carbon atoms and preferably from 1 to 5carbon atoms. When the alkyl groups are branched, the groups oftencomprise up to 10 branched chain carbon atoms, preferably up to 4branched chain atoms. Examples of alkylene chains which may berepresented by L include —CH₂—, —CH₂CH₂—, —(CH₂)₃—, —CH₂CH(CH₃)—, and—CH₂C(CH₃)₂— chains.

Ether and polyether bridging units which may be represented by L includelinear and branched alkylene-oxy-alkylene chains orpoly(alkyleneoxy)-alkylene chains comprising up to 150 carbon atoms andup to 40 oxygen atoms, particularly from 2 to 15 carbon atoms and from 1to 4 oxygen atoms, and preferably from 2 to 6 carbon atoms and from 1 to2 oxygen atoms. Examples of alkylene-oxy-alkylene chains orpoly(alkyleneoxy)-alkylene chains which may be represented by L include—CH₂—O—CH₂—, —CH₂CH₂—O—CH₂CH₂—, —(CH₂)₃—O—(CH₂)₃—,—CH₂CH(CH₃)—O—CH₂CH₂—, —CH₂CH(CH₃)—O—CH₂CH(CH₃)— chains, and also—[CH₂CH₂—O]_(n)—CH₂CH₂— and —[CH₂CH(CH₃)—O]_(n)—CH₂CH(CH₃)— chains wheren=2, 3 or 4.

Cyclic bridging units which may be represented by L include aromatic,saturated and partially unsaturated ring systems and may constitute 1ring or 2 or more fused rings which may include cycloalkyl, aryl orheterocyclic rings. In certain embodiments, cycloalkyl and aryl ringscommonly comprise from 3 to 10 carbon atoms in the largest ring, andheterocyclic rings commonly comprise from 3 to 7 ring atoms in which atleast one atom is carbon and at least one atom is any of N, O, S or P.Examples of aromatic, saturated and partially unsaturated ring systemswhich may be represented by L include —CH₂C₆H₄CH₂— and —CH₂C₆H₁₀CH₂—.

Examples of functionalised monomers comprising pendant 1,3-ketoester or1,3-ketoamide groups include:

In certain highly preferred embodiments, the functionalised monomercomprising pendant 1,3-ketoester or 1,3-ketoamide groups attached bymeans of a linker to a single monomer type is acetoacetoxyethylmethacrylate having the formula:

In a preferred embodiment, functional supports are derived from thepolymerisation of compositions comprising a functionalised monomercomprising pendant 1,3-ketoester or 1,3-ketoamide groups selected fromthe group consisting of monomers having the formulae:

and one or more monomers selected from the group consisting of styreneand substituted styrenes, such as α-methyl styrene, methyl styrene,t-butyl styrene, bromo styrene and acetoxy styrene; alkyl esters ofmono-olefinically unsaturated dicarboxylic acids, such as di-n-butylmaleate and di-n-butyl fumarate; vinyl esters of carboxylic acids suchas vinyl acetate, vinyl propionate, vinyl laurate and vinyl esters ofversatic acid such as VeoVa 9 and VeoVa 10 (VeoVa is a trademark ofShell); acrylamides such as methyl acrylamide and ethyl acrylamide;methacrylamides such as methyl methacrylamide and ethyl methacrylamide;nitrile monomers such as acrylonitrile and methacrylonitrile; esters ofacrylic and methacrylic acid, preferably optionally substitutedC₁₋₂₀alkyl and C₁₋₂₀cycloalkyl esters of acrylic and methacrylic acid,such as methyl acrylate, ethyl acrylate, n-butyl acrylate, 2-ethylhexylacrylate, i-propyl acrylate, and n-propyl acrylate, methyl methacrylate,ethyl methacrylate, n-butyl methacrylate, 2-ethylhexyl methacrylate,i-propyl methacrylate, n-propyl acrylate, hydroxyethyl acrylate,hydroxyethyl methacrylate, N,N-dimethylaminoethyl acrylate andN,N-dimethylaminoethyl methacrylate; divinylbenzene; trivinylbenzene;and multifunctional acrylates and methacrylates such as ethylene glycoldiacrylate, ethylene glycol dimethacrylate, trimethylolpropanetriacrylate, trimethylolpropane trimethacrylate, ethylene bisacrylamide,pentaerythritol triacrylate, pentaerythritol tetraacrylate,pentaerythritol trimethacrylate, pentaerythritol tetramethacrylate andN,N-bis-acryloyl ethylene diamine.

In a more preferred embodiment, functional supports are derived from thepolymerisation of compositions comprising one or more monomers selectedfrom the group consisting of acetoacetoxyethyl acrylate,acetoacetoxyethyl methacrylate, acetoacetoxypropyl acrylate, andacetoacetoxypropyl methacrylate, one or more monomers selected from thegroup consisting of styrene, methyl acrylate, ethyl acrylate, methylmethacrylate, ethyl acrylate, and one or more monomers selected from thegroup consisting of divinylbenzene, trivinylbenzene ethylene glycoldiacrylate, ethylene glycol dimethacrylate, trimethylolpropanetriacrylate, trimethylolpropane trimethacrylate, ethylene bisacrylamide,pentaerythritol triacrylate, pentaerythritol tetraacrylate,pentaerythritol trimethacrylate, pentaerythritol tetramethacrylate andN,N-bis-acryloyl ethylene diamine.

In a highly preferred embodiment, functional supports are derived fromthe polymerisation of compositions comprising acetoacetoxyethylmethacrylate, styrene and divinylbenzene.

Where the functional support is derived from the polymerisation of acomposition comprising one or two monomers containing only onepolymerisable double bonds, one monomer containing two or threepolymerisable double bonds, and a functionalised monomer of generalformula (2), the mole ratio of the total number of moles of monomerscontaining only one polymerisable double bonds:functionalised monomer ofgeneral formula (2) may be from 100:1 to 1:100, is preferably from 70:30to 1:99 and most preferably is from 60:40 to 15:85. The level ofcrosslinking, as defined herein above, may be from 0.5% to 80%,preferably from 1% to 60% and most preferably from 1% to 40%.

When the functional support is derived from the polymerisation ofstyrene, divinylbenzene and a functionalised monomer of general formula(2), the mole ratio of styrene:functionalised monomer of general formula(2) is often from 100:1 to 1:100, is preferably from 70:30 to 1:99 andmost preferably is from 60:40 to 15:85. The level of crosslinking isoften from 0.5% to 80%, preferably from 1% to 60% and most preferablyfrom 1% to 40%.

Functional supports prepared from functionalised monomers comprisingpendant 1,3-ketoester or 1,3-ketoamide groups are preferably produced asbeads. The beads often range in size from diameters of 10 μm to 2000 μm,preferably from 50 μm to 1000 μm, and most preferably from 75 μm to 500μm.

The functional supports may be prepared by an aqueous suspensionpolymerisation process, for example as described in Journal of AppliedPolymer Science, 1982, 27, 133-138. The monomers can be suspended asdroplets often of diameter from 1 μm to 1000 μm in water. Preferablystabilisers are added to prevent agglomeration of the droplets. Examplesof stabilisers which may be added include polyvinyl alcohol, polyacrylicacid, polyvinyl pyrrolidone, polyalkylene oxide, barium sulphate,magnesium sulphate and sodium sulphate. Agitation of the suspension ispreferably employed. The method of agitation employed may help to assistin maintaining the suspension. A free radical initiator commonly servesto initiate polymerisation. The free radical initiator employed isselected according to the types of monomers present. Examples of freeradical initiators which may be used to prepare scavenger supports whichmay be employed in processes of the present invention include benzoylperoxide, dioctanoyl peroxide, dilauroyl peroxide,2,2′-azobisisobutyronitnle and 2,2′-azobis(2,4-dimethylvaleronitrile).The selection of a suitable temperature range may be influenced by thenature of the monomers and the initiator present. Polymerisation of themonomers is commonly carried out at temperatures ranging from 15 to 160°C., preferably from 50 to 90° C. The resultant functional support may beisolated by filtration, optionally washed with one or more solvents.Suitable solvents for washing the scavenger support includetetrahydrofuran, methanol and water. The resultant functional supportmay be dried and the beads classified according to size by for examplesieving.

Amines that may be reacted with the pendent 1,3-ketoester or1,3-ketoamide pendant groups of the functional support includeoptionally substituted primary and secondary amines, optionallysubstituted hydrazines or salts thereof. The optionally substitutedprimary and secondary amine may include mono-amines, di-amine andpolyamines. The optionally substituted primary and secondary amine,preferably is an amine of formula HNR⁴R⁵ or a hydrazine of formulaH₂NNR⁴R⁵ wherein R⁴ is a substituent group and R⁵ is hydrogen or asubstituent group, or R⁴ and R⁵ may optionally be linked in such a wayso as to form an optionally substituted heterocyclic ring. Substituentgroups which may be represented by R⁴ and R⁵ independently includeoptionally substituted hydrocarbyl groups and optionally substitutedheterocyclyl groups as defined for R¹, sulphonyl groups such as SO₂R^(a)where R^(a) is an optionally substituted hydrocarbyl group or anoptionally substituted heterocyclyl group as defined for R¹, acyl groupssuch as COR^(b), CO₂H, or CO₂R^(b) groups where R^(b) is an optionallysubstituted hydrocarbyl group or an optionally substituted heterocyclylgroup as defined for R¹, and thioacyl groups such CSR^(c), CS₂H, CSNH₂,CS₂R^(c) or CSNHR^(c) groups where R^(c) is an optionally substitutedhydrocarbyl group or an optionally substituted heterocyclyl group asdefined for R¹. When R⁴ or R⁵ is an optionally substituted hydrocarbylgroups and optionally substituted heterocyclyl groups, the optionalsubstituents include optional substituents defined for R¹ and sulphonylgroups such as SO₂R^(a) where R^(a) is an optionally substitutedhydrocarbyl group or an optionally substituted heterocyclyl group asdefined for R¹, acyl groups such as COR^(b), CO₂H, or CO₂R^(b) groupswhere R^(b) is an optionally substituted hydrocarbyl group or anoptionally substituted heterocyclyl group as defined for R¹, andthioacyl groups such CSR^(c), CS₂H, CSNH₂, CS₂R^(c) or CSNHR^(c) groupswhere R^(c) is an optionally substituted hydrocarbyl group or anoptionally substituted heterocyclyl group as defined for R¹, andparticularly were the sulphonyl, acyl or thioacyl groups substituteamino groups of amino substituted hydrocarbyl groups. Preferably, R⁴ isan optionally substituted hydrocarbyl group or an optionally substitutedheterocyclyl group.

Examples of amines include:

Highly preferred amines are:

The scavenger support obtainable by the reaction of a functionalisedsupport comprising pendant groups selected from 1,3-ketoesters or1,3-ketoamides or mixtures thereof attached to a polymer support with anamine is preferably a scavenger support comprising pendant groupsselected from 3-iminoesters, 3-iminoamides, 2,3-enaminoesters or2,3-enaminoamides or mixtures thereof attached to a polymer support.

The 3-iminoesters, 3-iminoamides, 2,3-enaminoesters or 2,3-enaminoamidespendant groups includes groups of Formula (3) or (4):

wherein

-   -   R¹ is an optionally substituted hydrocarbyl, perhalogenated        hydrocarbyl or heterocyclyl group;    -   X is O or NR², wherein the free valence of O or NR² is bonded to        a polymer support optionally via a linker;    -   R² is hydrogen, an optionally substituted hydrocarbyl, or        heterocyclyl group;    -   R⁴ is a substituent group; and    -   R⁵ is hydrogen or a substituent group, or R⁴ and R⁵ may        optionally be linked in such a way so as to form an optionally        substituted heterocyclic ring,        or tautomers or salts thereof.

The scavenger support used in the process of the present invention maybe prepared by reacting the amine with the functional support comprisingketoester or ketoamide groups before or after contact with the metalcontaining solution. In the case that the amine is reacted with thefunctional support after contact with the metal containing solution, thesolution containing the metal may be contacted first with the amine or asolution containing the amine and then brought into contact with thefunctional support, or the solution containing the metal may becontacted first with the functional support and then brought intocontact with the amine or a solution containing the amine. Preferablythe amine is reacted with the functional support to give a scavengersupport containing groups according to Formula (3) or (4) before contactwith the metal containing solution.

The scavenger support used in the process of the present invention maybe prepared by contacting the amine with the functional support at atemperature between −100 to 250° C., preferably from −10 to 100° C.,more preferably from 10 to 80° C. and most preferably at 15 to 70° C.

The scavenger support used in the process of the present invention maybe prepared by contacting the amine with the functional support in thepresence of a solvent. Suitable solvents include any solvent which iscompatible with the functional support. Suitable solvents include anysolvents that when the functional support is based on a crosslinkedresin are capable of swelling the crosslinked resin or any solvents thatwhen the functional support is based on a macroporous resins are capableof entering the pores of the macroporous resin. Suitable solvents may beselected from polar, non-polar, protic and aprotic solvents. Examples ofsuitable solvents include aliphatic hydrocarbons such as hexane andheptane, aromatic hydrocarbons such as toluene and xylene, chlorinatedhydrocarbons such as dichloromethane (DCM), and chloroform, ethers suchas diethyl ether, methyl-tert-butyl ether and tetrahydrofuran (THF),esters such as ethyl acetate and isopropyl acetate, ketones such asacetone and methyl ethyl ketone, dipolar aprotic solvents such asN,N-dimethylformamide (DMF), dimethylsulphoxide (DMSO) andN-methylpyrrolidinone (NMP), nitriles such as acetonitrile andpropionitrile, alcohols such as methanol and propan-2-ol, and water andmixtures thereof. Preferred solvents include hexane, toluene, THF, DCM,chloroform, DMF, NMP, pyridine, acetone, ethyl acetate, methyl tertiarybutyl ether, ethanol, water and mixtures thereof. In the case offunctionalised supports based on microporous resins a suitable solventcapable of swelling the resin may be used. Preferred solvents forswellable resins include toluene, THF, DCM, chloroform, DMF, NMP,pyridine, acetone, ethyl acetate, ethanol and mixtures thereof. Wherefunctional supports based on macroporous resin are employed, a solventmay not be required and undiluted amine may be contacted with thefunctional support.

The scavenger support used in the process of the present invention maybe prepared by contacting the amine with the functional supportoptionally in the presence of a catalyst. Catalysts include catalystswhich are known to promote the reaction of a ketoester or ketoamide withan amine such as silica, dehydrating agents, acids and metal salts.Preferably the catalyst is an acid such as acetic acid, methanesulphonicacid, benzenesulphonic acid, p-toluenesulphonic acid, hydrochloric acidor sulphuric acid, or a metal salt such as magnesium sulphate, lithiumperchlorate or zinc perchlorate.

The scavenger support used in the process of the present invention maybe prepared by contacting the amine with the functional support for atime sufficient to react at least a portion of the ketoester orketoamide groups with the amine. The ratio of molar concentration ofketoester or ketoamide functionality on the scavenger support to molarconcentration of amine may be in the range from 1:100 to 100:1.Preferably an excess of amine is employed, for example ratios in therange of 1:1 to 20:1 or more preferably in the range of 1:1 to 4:1.

In a further preferred aspect of the present invention the scavengersupport prepared by reacting an amine with a functional support, asrepresented by formula (3) or (4), may be further chemically modifiedbefore use.

Chemical modifications may be performed with any compound capable ofreacting with an amine including carboxylic acids, carboxylic acidanhydrides, carboxylic esters and thioesters, acyl halides, sulphonylhalides (to sulphonamides), epoxides, haloalkyl compounds, includinghaloalkylcarboxylates (alkylation of the amine), sulphonyl esters(alkylation of the amine), carbon disulphide, ketones, aldehydes,isocyanantes and isothiocyanates. One or more chemical modifications maybe performed.

Preferably the scavenger support which is chemically modified before useis a scavenger support obtainable by reacting a functionalised supportwith an amine containing more than one amine group. Scavenger supportsobtainable in this manner are scavenger supports comprising multi-aminefunctionality wherein at least a portion of the amine functionalitycomprises amine groups which are susceptible to further chemicalmodification. Preferably, the scavenger support comprising multi-aminefunctionality comprises a mixture of primary and secondary aminefunctionality. The chemical modification of the amine groups of thescavenger support with multi-amine functionality may be partial orcomplete.

In certain preferred embodiments, a functional support comprisingketoester or ketoamide groups is reacted with a tri-amine, such asdiethylene tri-amine, then contacted with a reagent which will furtherreact with amines which are present, such as carbon disulphide, anisothiocyanate, or a haloacetate, for example chloroacetic acid orsalts, esters or acid chlorides thereof. Preferably, an excess oftri-amine is used to encourage reaction of a single tri-amine with asingle pendant ketoester or ketoamide therefore reducing the number ofpossible chains tethered at both ends.

It is postulated that when the scavenger support with multi-aminefunctionality is contacted with a reagent which will further react withan amine, that contacting with carbon disulphide results in theformation of dithiocarbamate groups or salts thereof, that contactingwith an isothiocyanate, results in formation of thiourea groups or saltsthereof, or that contacting with chloroacetic acid or salts, esters oracid chlorides thereof results in the formation of aminoacetate groupsor salts thereof.

In another preferred embodiment an alkene functional amine is reactedwith the ketoester or ketoamide support and then further functionalisedwith a difunctional phosphine.

Examples of scavenger supports which are chemically modified before useinclude:

wherein R is an optionally substituted hydrocarbyl and X is a support asdescribed herein before.

When the scavenger supports described hereinbefore above are used tobind metals, for example in the process according to the first aspect ofthe present invention, the resulting support bound metal compositionsare new. These support bound metal compositions may find use as reagentsor catalysts.

According to a further aspect of the present invention there is provideda support bound metal composition obtainable by contacting a solutioncomprising a metal is with a scavenger support, whereby the scavengersupport binds to at least some of the metal in solution therebydecreasing the amount of metal in solution, characterised in that thescavenger support comprises a functionalised support comprising pendantgroups selected from 1,3-ketoesters or 1,3-ketoamides or mixturesthereof attached to a support wherein a number of the pendant groups arereacted with an amine.

Metals, solutions comprising a metal and scavenger supports are asdescribed hereinbefore above.

The invention is further illustrated, but not limited, by the followingexamples.

EXAMPLES Example 1 Preparation of Enaminoester Containing Supports 1-12Using Nucleophilic Amines

2.0 g, (4 mmol) of a resin prepared from acetoacetoxyethyl methacrylate(MEM), styrene and 1 wt % divinylbenzene (as taught in patentapplication WO0198378) containing 2.0 mmol/g of acetoacetoxyfunctionality was charged to a large vial. Tetrahydrofuran (THF) (20 ml)was added and the resin left to swell for 1 hour. Amine-containingcompound (12 mmol, 3 equivalents) was then added, the vial was stopperedand the mixture left to agitate on a roller for 18 hours. The resin wasfiltered through a sinter and then washed with THF (5×20 ml),THF/methanol 50/50 (10×20 ml) and methanol (5×20 ml). The resin wasdried to a constant weight at room temperature under vacuum. Loadingvalues were calculated from elemental analysis of nitrogen content. Theresins produced are detailed in Table 1.

TABLE 1 Resins produced by reaction of 1% DVB Ketoester resin withnucleophilic amines Scavenger Loading of resin Amine (from producedAmine used % N), mmol/g 1 Butylamine

1.57 2 Benzylamine

0.93 3 Ethylene- diamine

1.61 4 Diethylene- triamine

1.36 5 Triethylene- tetramine

1.2  6 Tris-(2-amino- ethyl)amine

1.27 7 Poly(ethylene- imine) 1200

8 mmol/g of nitrogen 8 Triethoxy-3- aminopropyl- silane

1.36 9 4- Aminomethyl pyridine

1.64 10 1-(3-amino- propyl)- imidazole

1.55 11 Thiophene-2- methylamine

0.71 12 3- Aminopropyl- diphenyl- phosphine

0.57

Example 2 Preparation of Enaminoester Containing Supports 13 and 14Using Aromatic Amines

2.0 g (4 mmol) of a resin prepared from acetoacetoxyethyl methacrylate,styrene and 1 mol % divinylbenzene (as taught in patent applicationWO0198378) containing 2.0 mmol/g of acetoacetoxy functionality wascharged to a 100 ml 4 necked round-bottomed flask fitted with a stirrer,temperature probe and condenser. THF (20 mls) was added and the resinallowed to swell for 30 minutes. 2-Aminothiophenol or 4-aminothiphenol(1.502 g, 12 mmol, 3 equivalents) and p-toluenesulphonic acid (50 mg,0.29 mmol, 0.07 equivalents) were added to the stirred suspension. Thereaction mixture was heated to reflux (67° C.) and maintained at thistemperature for a further 5 hours. The mixture was cooled to roomtemperature, the resin filtered on a glass sinter funnel andsubsequently washed with THF (5×20 ml), THF/methanol 50/50 (10×20 ml)and methanol (5×20 ml). The resin was dried to a constant weight at 40°C. under vacuum. Loading values were calculated from elemental analysisof nitrogen and sulphur content. The resins produced are detailed inTable 2.

TABLE 2 Resins produced by reaction of 1% DVB Ketoester resin witharomatic amines Scavenger Loading of Amine resin produced Amine used(from % S), mmol/g 13 2-aminothiophenol

1.57 14 4-aminothiophenol

1.64

Example 3 Preparation of Resin 15 Derived from Reaction ofPhenylthiosemicarbazide and Ketoester Resin

2.0 g, (4 mmol) of a resin prepared from acetoacetoxyethyl methacrylate,styrene and 1 mol % divinylbenzene (as taught in patent applicationWO0198378) containing 2.0 mmol/g of acetoacetoxy functionality wascharged to a 100 ml 4 necked round-bottomed flask fitted with a stirrer,temperature probe and condenser. THF (20 mls) was added and the resinallowed to swell for 30 minutes. 4-Phenyl-3-thiosemicarbazide (2.0 g, 12mmol, 3 equivalents) was dissolved in a mixture of ethanol and THF(50:50 vol:vol, 20 ml) and the solution added to the swollen resin.p-toluenesulphonic acid (50 mg, 0.29 mmol, 0.07 equivalents) was addedto the flask, the reaction mixture was heated to reflux (67° C.) andmaintained at this temperature for a further 5 hours. The mixture wascooled to room temperature, the resin filtered on a glass sinter funneland subsequently washed with THF (5×20 ml), THF/methanol 50/50 (10×20ml) and methanol (5×20 ml). The resin was dried to a constant weight at40° C. under vacuum. Loading values were calculated from elementalanalysis of nitrogen and sulphur content. The resin produced is detailedin Table 3.

TABLE 3 Resin produced by reaction of 1% DVB Ketoester resin withphenylthiosemicarbazide Scavenger Loading of Amine resin produced Amineused (from % N), mmol/g 15 Phenylthiosemicarbazide

1.43

Example 4 Chemical Modification of AAEM-DETA Resin 4

4.1 Reaction with Carbon Disulphide to give Resin 16

MEM-DTA resin 4 (3.0 g, 1.36 mmol/g, 4.08 mmol) was charged to a 100 mlflask fitted with a stirrer, temperature probe and condenser. Anhydrousdichloromethane (DCM) (30 ml) was added and the suspension cooled to 0°C. Carbon disulphide (0.621 g, 8.16 mmol, 2 equivalents) was charged tothe stirred suspension followed by triethylamine (0.826 g, 8 mmol, 2equivalents). The reaction mixture was left to stir at 0-5° C. for 1hour and the reaction mixture allowed to warm to room temperature. Thereaction was then heated to reflux for 4 hours, cooled and the resinfiltered off. The resin was washed with DCM, (5×20 ml), DCM/methanol50/50 (10×20 ml) and methanol (5×20 ml) and dried to a constant weightat 40° C. under vacuum. Loading values were calculated from elementalanalysis of nitrogen and sulphur content. The resin produced is detailedin Table 4.

4.2 Reaction with Hexylthioisocyanate to Give Resin 17

MEM-DTA resin 4 (2.0 g, 1.36 mmol/g, 2.72 mmol) was charged to a largevial. Anhydrous THF (20 mls) was added and the resin allowed to swellfor 30 minutes. Hexylthioisocyanate (1.946 g, 13.6 mmol, 5 equivalents)was added, the vial sealed and agitated on a roller for 48 hours at roomtemperature. The reaction mixture was filtered and the resin washed withTHF (5×20 ml) and diethyl ether (5×20 ml), then dried to a constantweight at 40° C. under vacuum. Loading values were calculated fromelemental analysis of nitrogen and sulphur content. The resin producedis detailed in Table 4.

TABLE 4 Resins produced by chemical modification of AAEM-DETA resin 4Scavenger resin Loading (from produced Modification of AAEM resin % S),mmol/g 16 Diethylene triamine modified with carbon disulphide

1.53 mmol/g dithiocarbamate 17 Diethylene triamine modified withhexylthioiso- cyanate

1.47 mmol/g thiourea groups

Example 5 Preparation of Enaminoester Containing Supports 18-19 Using aMacroporous AAEM Resin

2.0 g, (4.6 mmol) of a macroporous resin containing a total of 2.3mmol/g of acetoacetoxy functionality (prepared from AAEM and 40 wt %divinylbenzene using as porogen a 30% polystyrene (molecular weight50000) in toluene solution at 40% on total organic phase, as taught inpatent application WO0198378) was charged to a large vial. THF (20 ml)was added and the resin left to swell for 1 hour. Amine-containingcompound (12 mmol, 3 equivalents) was then added, the vial was stopperedand the mixture left to agitate on a roller for 18 hours. The resin wasfiltered through a sinter and then washed with THF (5×20 ml),THF/methanol 50/50 (10×20 ml) and methanol (5×20 ml). The resin wasdried to a constant weight at room temperature under vacuum. Loadingvalues were calculated from elemental analysis of nitrogen content. Theresins produced are detailed in Table

Scavenger resin Loading of Amine produced Amine used (from % N), mmol/g18 Macroporous AAEM/ethylene diamine

1.25 19 Macroporous AAEM/diethylene triamine

1.00

Example 6 Preparation of Enaminoamide Containing Support 20 Using aMicroporous Amino Functional Resin

50 ml anhydrous DCM was added to 5.0 g of an aminomethylpolystyreneresin (Biotherm BT-3100 100-200 mesh, ca 1.4 mmol/g, 6.8 mmol) undernitrogen, allowed to swell at room temperature for 30 minutes, thencooled with stirring to −5° C. Diketene (2.62 ml, 34 mmol, 5equivalents) was dissolved in anhydrous 5 ml DCM and then slowly addedto the stirred resin whilst maintaining the reaction temperature at −15to −20° C. The mixture was allowed to stir at this temperature for 2hours before allowing to warm to room temperature and stirring for afurther 18 hours. The resin was filtered off from the solution andwashed with DCM (5×50 ml), DCM/methanol (10×50 ml) and methanol (5×50ml), and dried in a vacuum oven at 40° C. overnight, resulting in 5.49 gof beads with a negative Kaiser test (qualitative colourimetric test forprimary amines, involving incubating ca 5 mg of the resin with 4 dropsof 5% ninhydrin in ethanol, 2 drops of 80% phenol in ethanol, 2 drops ofpyridine (dried)), indicating all the amine functionality had reactedaccording to the following reaction scheme:

1 g of the ketoamide resin thus produced was swollen with THF (10 ml)for 30 minutes then treated with diethylene triamine (0.421 g, 4.1 mmol,3 equivalents on theoretical loading) and agitated for 18 hours. Theresin was filtered off and washed with THF (5×10 ml), THF/methanol 50/50(10×10 ml) and methanol (5×10 ml). The resin was dried to a constantweight at room temperature under vacuum to give support 20.

Example 7 Preparation of a Ketoester Functional Support 21 Prepared froma Microporous Amino Functional Resin and a Multifunctional Ketoester

50 ml anhydrous THF was added to 5.0 g of an aminomethylpolystyreneresin (Biotherm BT-3100 100-200 mesh, ca 1.4 mmol/g, 6.8 mmol) undernitrogen and allowed to swell at room temperature for 30 minutes.Trimethylolpropane triacetoacetate (Lonzamon AATMP, 7.88 g, 20 mmol, 3equivalents) was added to the mixture and left to react for 18 hours atroom temperature. The resin was filtered off from the solution andwashed with DCM (5×50 ml), DCM/methanol (10×50 ml) and methanol (5×50ml), and dried in a vacuum oven at 40° C. overnight, resulting in 5.99 gof beads with a very weak positive Kaiser test, indicating most of theamine functionality had reacted according to the following scheme:

1 g of the resin thus produced was swollen with THF (10 ml) for 30minutes then treated with diethylene triamine (1.263 g, 12.2 mmol, 4.5equivalents on theoretical maximum loading of ketoester) and agitatedfor 18 hours. The resin was filtered off and washed with THF (5×10 ml),THF/methanol 50/50 (10×10 ml) and methanol (5×10 ml). The resin wasdried to a constant weight at room temperature under vacuum to givesupport 21.

Example 8 Preparation of Enaminoamide Containing Support 22 Using anAmino Functional Silica Gel

40 ml anhydrous DCM was added to 5.0 g of an aminopropyl functionalsilica (surface area 650 m2/g, 7.2% C content) and cooled with overheadstirring to −15° C. Diketene (2.396 g) in DCM (5 ml) was added slowlywhilst keeping the temperature between −15 and −20° C., and the mixturestirred at this temperature for 2 hrs before warming to roomtemperature. After a further 18 hours the silica was filtered off,washed with DCM (10×40 ml) and diethyl ether (5×40 ml) then dried in avacuum oven at 40° C. to constant weight. This yielded 5.129 g of silicawith a negative Kaiser test for primary amines, indicating the amineshad reacted according to the following scheme:

1.0 g of the silica thus produced was treated with diethylene triamine(0.353 g) in THF (10 ml) and agitated at room temperature for 18 hours.The silica was filtered off, washed with THF (5×10 ml) THF/methanol 1:1(10×5 ml) and methanol (5×10 ml) then dried in a vacuum oven at 40° C.to constant weight, yielding 1.0 g of support 22.

Scavenger support Loading of Amine produced Support structure (from %N), mmol/g 20

0.52 21

0.60 22

0.48

Example 9 Scavenging of Palladium from Organic Solutions

Seven solutions were made up containing palladium salts with and withoutadditional compounds. Palladium(II) acetate was dissolved in 3 separatesingle solvents: dichloromethane, N,N-dimethylformamide andtetrahydrofuran. Palladium(II) acetate was also dissolved in a 9:1vol/vol mixture of DCM and triethylamine. A solution of palladium(II)chloride was made up in THF. Tris(dibenzylideneacetone)dipalladium(0)(Pd2(dba)3) was dissolved in DCM. Palladium(II) acetate and 4equivalents of triphenylphosphine were dissolved in DCM.

Typical amounts of reagents used to make up the solutions, targeting1000 or 500 ppm are shown below:

Solvent Target Pd Palladium (made up to level (ppm source Mass (g)Additive and amount 100 ml) wt/vol) Pd(OAc)2 0.218 — DCM 1000 Pd(OAc)20.218 — DMF 1000 Pd(OAc)2 0.218 — THF 1000 Pd(OAc)2 0.218 Triethylamine,10 ml DCM 1000 PdCl2 5 ml of a — THF 500 standard 1% Pd w/v solution inTHF Pd2(dba)3 0.215 — DCM 500 Pd(OAc)2 0.218 Triphenylphosphine, DCM1000 1.02 g (4 equiv on Pd)

Some solutions were made up targeting a lower level of palladium thangiven in this table.

Efficacy tests were carded out by mixing a quantity of the test resinwith a 10 ml aliquot of the solution in a sealed vial and agitated on aroller for 16 hours.

For the Comparative Examples using Smopex 110 (isothiouroniumfunctionality), Smopex 111 (thiol functionality) (both obtained fromJohnson Matthey Inc.) and Chelex 100 (iminodiacetate functionality,obtained from Fluka), the quantity of resin used was 16 molarequivalents of functionality per molar equivalent of metal.

For the Resins 1-19 and 22, the quantity of resin used was 4 molarequivalents of the enamine on the resin per molar equivalent of metal.

For example 0.240 g of resin 1 (1.57 mmol/g, 377 μmol enamine) was usedfor 10 mls of a 1000 ppm wt/vol Pd solution of palladium acetate in DCM(94 μmol Pd). The resin was filtered off and the solution subjected topalladium analysis.

In addition, AAEM, a ketoester resin, which is the functional supportused in the preparation of scavenger supports of Examples 1-4 andMP-AAEM a ketoester resin, which is the functional support used in thepreparation of scavenger supports of Example 5 were also tested andrepresent Control Examples of non-amine functionalised supports.

The solutions (including the starting solutions) were tested forpalladium by ICP-AES (Inductively Coupled Plasma—Atomic EmissionSpectroscopy). The solvent was first removed by evaporation and theresidues were digested in nitric/sulphuric acid mixture. The results areexpressed as parts per million wt/wt of palladium in solution, and asthe percent reduction of palladium in solution after scavenging. Theresults are shown in Tables 9.1-9.7.

In Table 9.1, the resins prepared in Examples 1-19 and 22, scavengersupports of the present invention, are shown to be more effective atremoving palladium from solution than the Control (non-aminefunctionalised resins) and the Comparative Examples.

In Table 9.2-9.6, several scavenger supports of the present inventionare shown to be effective in removing palladium from solutionscontaining species, such as DMF, triethylamine and triphenylphosphinewhich are all known to coordinate to palladium in solution. (Note:triethylamine and particularly triphenylphosphine are known to beparticularly strong coordinators).

TABLE 9.1 Pd(OAc)2 in DCM (yellow-brown solution) Pd level Pd levelBefore After % Support (ppm) (ppm) reduction Smopex 110 790 670 15.2Smopex 111 790 135 82.9 Chelex 100 405 390 3.7 AAEM 790 815 0.00 MP-AAEM790 760 3.80  1 785 9 98.85  2 410 1 99.76  3 755 3 99.60  4 755<1 >99.87  5 755 1 99.87  6 745 1 99.87  7 755 1 99.87  8 775 10 98.71 9 405 <1 >99.75 10 755 <1 >99.87 11 785 <1 >99.87 12 785 Colourless* 13405 <1 >99.75 14 410 <1 >99.76 15 410 <1 >99.76 16 755 11 98.54 17 755 199.87 18 775 3 99.61 19 775 68 91.23 22 395 <1 >99.75

Smopex 110, Smopex 111 and Chelex 100 are Comparative Examples.

AAEM is the ketoester resin used for reaction with amines in Examples1-4 and MP-AAEM is the resin used for reaction with amines in Example 5.These are Control Experiments and are Examples of non-aminefunctionalised resins.

No quantitative data was obtained for resin 12, colouration indicateshigh level of scavenging.

TABLE 9.2 Pd(OAc)2 in DMF Pd level Pd level Before After % Support (ppm)(ppm) reduction 1 530 22 95.85 3 1065 31 97.09 4 530 120 77.36 5 530 21060.38 11 530 <1 >99.81 13 530 1 99.81 15 530 3 99.43 17 530 61 88.49

TABLE 9.3 Pd(OAc)2 in THF Pd level Pd level Before After % Support (ppm)(ppm) reduction 3 545 10 98.17 4 1115 290 73.99 5 545 145 73.39 9 545 1397.61 11 1115 1 99.91 13 1115 <1 >99.91 16 1115 155 86.10 17 1115 <1>99.91

TABLE 9.4 Pd(OAc)₂ in 9:1 DCM:Et3N Pd level Pd level Before After %Support (ppm) (ppm) reduction 3 780 18 97.69 4 780 8 98.97 5 780 9 98.857 780 170 78.21 11 415 20 95.18 13 415 17 95.90 17 415 12 97.11

TABLE 9.5 PdCl₂ in THF Pd level Pd level Before After % Support (ppm)(ppm) reduction 3 655 25 96.18 4 655 33 94.96 5 655 10 98.47 6 655 3794.35 7 655 <1 >99.85 9 655 205 68.70

TABLE 9.6 Pd₂(dba)₃ in DCM (deep purple solution) Pd level Before Pdlevel % Support (ppm) After (ppm) reduction 4 195 <1 >99.49 5 165<1 >99.39 6 165 <1 >99.39 11 195 <1 >99.49 13 195 <1 >99.49 15 165<1 >99.39 17 195 <1 >99.49 20 Pale yellow* 21 Pale yellow* 22 340 <1>99.7

TABLE 9.7 Pd(OAc)₂/PPh₃ in DCM (Dark brown solution) Pd level Before Pdlevel % Support (ppm) After (ppm) reduction 4 360 12 96.67 5 290 6 97.936 290 62 78.62 11 360 115 68.06 13 360 2 99.44 15 290 61 78.97 17 360 4188.61 20 Colourless* 21 Colourless* 22 400 <1 >99.75 *No quantitativedata obtained - colouration indicates high level of scavenging

Example 10 Scavenging of Metal from Organic Solutions of Other MetalComplexes

In order to demonstrate the efficacy of supports of the invention asscavengers for metals other than palladium a variety of other transitionmetal solutions (cobalt, nickel, vanadium, rhodium and copper) were madeup as follows:

Solvent Target Mass (made up to Metal level Metal salt (g) 100 ml) (ppmwt/vol) CoCl₂(PPh₃)₂ 0.555 DCM 500 Ni(Acac)₂ 0.218 DCM 500 NiCl₂(PPh₃)₂0.557 DMF 500 OV(Acac)₂ 0.26 DCM 500 [Rh(OAc)₂]₂ 0.108 DMF 500 Cu(Acac)₂0.206 DCM 500

Efficacy tests were carried out by mixing a quantity of the test resinwith a 10 ml aliquot of the solution in a sealed vial and agitated on aroller for 16 hours. The quantity of resin used was 4 molar equivalentsof the enamine on the resin per molar equivalent of metal. The resultantsolutions were subjected to ICP-OES analysis in a similar manner toExample 8, by evaporation of solvent and digestion of the residue.

For example 0.21 g of resin 9 (1.64 mmol/g, 344 μmol enamine) was usedfor 10 mls of a 500 ppm wt/vol Co solution ofbis(triphenylphosphino)cobalt(II) chloride in DCM (85 μmol Co). Theresin was filtered off and the solution subjected to ICP analysis forcobalt.

The results are shown in Table 10. They demonstrate that the resins ofthe current invention demonstrate a high affinity for a wide variety oftransition metals in a variety of complexes.

TABLE 10 Metal level Metal level Before After % Support Metal Solution(ppm) (ppm) reduction 9 CoCl2(PPh3)2 in 115 <1 >99.1 DCM 11 CoCl2(PPh3)2in 115 <1 >99.1 DCM 11 Ni(Acac)2 in DCM 370 <1 >99.7 13 Ni(Acac)2 in DCM370 59 84.0 11 NiCl2(PPh3)2 in 520 4 99.2 DMF 11 OV(Acac)2 340 19 94.4 3[Rh(OAc)2]2 545 66 87.9 9 [Rh(OAc)2]2 545 <5 >99.1 11 [Rh(OAc)2]2 545<5 >99.1 13 Cu(Acac)2 390 <1 >99.7

The invention claimed is:
 1. A scavenger support obtained by reacting afunctionalised organic support comprising pendant groups selected from1,3-ketoesters or 1,3-ketoamides or mixtures thereof attached to asupport with an amine, wherein the scavenger support is adapted to be ascavenger, is insoluble and in a form suitable for filtration, and is inthe form of beads having a size in the range from 10 μm to 2000 μm, andthe amine is selected from the group consisting of: (i) an optionallysubstituted hydrazine or salt thereof; and (ii) an amine selected from:


2. A scavenger support according to claim 1 wherein the functionalisedsupport comprises pendant 1,3-ketoester or 1,3-ketoamide groups offormula 1:

wherein R¹ is an optionally substituted hydrocarbyl, perhalogenatedhydrocarbyl or heterocyclyl group; X is O or NR², wherein the freevalence of O or NR² is bonded to a support optionally via a linker; andR² is hydrogen, an optionally substituted hydrocarbyl, or heterocyclylgroup.
 3. A scavenger support according to claim 2 wherein thefunctionalised support comprising pendant groups selected from1,3-ketoesters or 1,3-ketoamides or mixtures thereof attached to asupport is obtained by reacting an amino functionalised polymer, with afunctionalising agent selected from ethylene glycol diacetoacetate,ethylene bisacetoacetamide, 1,1,1-tris(acetoacetoxymethyl)propane,diacetoacet-o-tolidide, diacetoacet-1,4-phenylenediamide,diacetoacet-2,5-dimethyl-1,4-phenylenediamide,diacetoacet-2-chloro-5-methyl-1,4-phenylenediamide,diacetoacet-2,5-dichloro-1,4-phenylenediamide, diketene, or2,2,6-trimethyl-4H-1,3-dioxin-4-one.
 4. A scavenger support according toclaim 2 wherein the functionalised support comprising pendant groupsselected from 1,3-ketoesters or 1,3-ketoamides or mixtures thereofattached to a support is obtained by polymerisation of a compositioncomprising a functionalised monomer comprising pendant 1,3-ketoester or1,3-ketoamide groups attached by means of a linker to a single monomertype.
 5. A scavenger support according to claim 4 wherein thefunctionalised support comprising pendant groups selected from1,3-ketoesters or 1,3-ketoamides or mixtures thereof attached to asupport is obtained by polymerisation of a composition comprising afunctionalised monomer comprising pendant 1,3-ketoester or 1,3-ketoamidegroups attached by means of a linker to a single monomer type, and oneor more monomers selected from the group consisting of styrene andsubstituted styrenes; alkyl esters of mono-olefinically unsaturateddicarboxylic acids; vinyl esters of carboxylic acids; acrylamides;methacrylamides; nitrile monomers; esters of acrylic and methacrylicacid; divinylbenzene; trivinylbenzene; and multifunctional acrylates andmethacrylates.
 6. A scavenger support according to claim 4 wherein thefunctionalised monomer comprising pendant 1,3-ketoester or 1,3-ketoamidegroups has the general formula 2:

wherein each X is independently 0 or NR²; R¹ and R² are as definedherein before above; R³ is H or an optionally substituted hydrocarbyl,perhalogenated hydrocarbyl or heterocyclyl group; and L is a linkinggroup.
 7. A scavenger support according to claim 6 wherein thefunctionalised monomer comprising pendant 1,3-ketoester or 1,3-ketoamidegroups has the general formula 2a:

wherein X is O or NR²; R¹ and R² are as defined herein before above; R³is H or an optionally substituted hydrocarbyl, perhalogenatedhydrocarbyl or heterocyclyl group; and L is a linking group.
 8. Ascavenger support according to claim 7 wherein the functional support isobtained by polymerisation of a composition comprising one or moremonomers selected from the group consisting of acetoacetoxyethylacrylate, acetoacetoxyethyl methacrylate, acetoacetoxypropyl acrylate,and acetoacetoxypropyl methacrylate, one or more monomers selected fromthe group consisting of styrene, methyl acrylate, ethyl acrylate, methylmethacrylate, ethyl acrylate, and one or more monomers selected from thegroup consisting of divinylbenzene, trivinylbenzene, ethylene glycoldiacrylate, ethylene glycol dimethacrylate, trimethylolpropanetriacrylate, trimethylolpropane trimethacrylate, ethylene bisacrylamide,pentaerythritol triacrylate, pentaerythritol tetraacrylate,pentaerythritol trimethacrylate, pentaerythritol tetramethacrylate andN,N-bis-acryloyl ethylene diamine.
 9. A scavenger support according toclaim 8 wherein the functional support is obtained by polymerisation ofcompositions comprising acetoacetoxyethyl methacrylate, styrene anddivinylbenzene.
 10. A scavenger support according to claim 1 wherein theamine is selected from


11. A scavenger support according to claim 1 wherein the scavengersupport is a scavenger support comprising pendant groups selected from3-iminoesters, 3-iminoamides, 2,3-enaminoesters or 2,3-enaminoamides ormixtures thereof attached to a polymer support.
 12. A scavenger supportaccording to claim 11 wherein the scavenger support comprises pendantgroups selected from 3-iminoesters, 3-iminoamides, 2,3-enaminoesters or2,3-enaminoamides of formula (3) or (4)

wherein R¹ is an optionally substituted hydrocarbyl, perhalogenatedhydrocarbyl or heterocyclyl group; X is O or NR², wherein the freevalence of O or NR² is bonded to a support optionally via a linker; R²is hydrogen, an optionally substituted hydrocarbyl, or heterocyclylgroup; R⁴ is a substituent group; and R⁵ is hydrogen or a substituentgroup, or R⁴ and R⁵ may optionally be linked in such as way so as toform an optionally substituted heterocyclic ring, or tautomers thereof.13. A scavenger support according to claim 1 wherein the amine is atri-amine.
 14. A scavenger support obtained by reacting the scavengersupport according to claim 13 with a reagent selected from carbondisulphide, an isothiocyanate, or a haloacetate.
 15. A scavenger supportobtained by reacting a functionalised inorganic support comprisingpendant groups selected from 1,3-ketoesters or 1,3-ketoamides ormixtures thereof attached to a support with an amine.
 16. A scavengersupport according to claim 15 wherein the functionalised supportcomprising pendant groups selected from 1,3-ketoesters or 1,3-ketoamidesor mixtures thereof attached to a support is obtained by reacting anamino functionalised silica with a functionalising agent selected fromethylene glycol diacetoacetate, ethylene bisacetoacetamide,1,1,1-tris(acetoacetoxymethyl)propane, diacetoacet-o-tolidide,diacetoacet-1,4-phenylenediamide,diacetoacet-2,5-dimethyl-1,4-phenylenediamide,diacetoacet-2-chloro-5-methyl-1,4-phenylenediamide,diacetoacet-2,5-dichloro-1,4-phenylenediamide, diketene, or2,2,6-trimethyl-4H-1,3-dioxin-4-one.
 17. A scavenger support accordingto claim 15 wherein the functionalised support comprises pendant1,3-ketoester or 1,3-ketoamide groups of formula 1:

wherein R¹ is an optionally substituted hydrocarbyl, perhalogenatedhydrocarbyl or heterocyclyl group; X is O or NR², wherein the freevalence of O or NR² is bonded to a support optionally via a linker; andR² is hydrogen, an optionally substituted hydrocarbyl, or heterocyclylgroup.
 18. A scavenger support according to claim 15 wherein the amineis an optionally substituted primary amine, an optionally substitutedsecondary amine, an optionally substituted hydrazine or salt thereof.19. A scavenger support according to claim 18 wherein the amine isselected from


20. A scavenger support according to claim 19 wherein the amine isselected from


21. A scavenger support according to claim 15 wherein the scavengersupport is a scavenger support comprising pendant groups selected from3-iminoesters, 3-iminoamides, 2,3-enaminoesters or 2,3-enaminoamides ormixtures thereof attached to a support.
 22. A scavenger supportaccording to claim 21 wherein the scavenger support comprises pendantgroups selected from 3-iminoesters, 3-iminoamides, 2,3-enaminoesters or2,3-enaminoamides of formula (3) or (4)

wherein R¹ is an optionally substituted hydrocarbyl, perhalogenatedhydrocarbyl or heterocyclyl group; X is O or NR², wherein the freevalence of O or NR² is bonded to a support optionally via a linker; R²is hydrogen, an optionally substituted hydrocarbyl, or heterocyclylgroup; R⁴ is a substituent group; and R⁵ is hydrogen or a substituentgroup, or R⁴ and R⁵ may optionally be linked in such as way so as toform an optionally substituted heterocyclic ring, or tautomers thereof.23. A scavenger support according to claim 15 wherein the amine is atri-amine.
 24. A scavenger support obtained by reacting the scavengersupport according to claim 23 with a reagent selected from carbondisulphide, an isothiocyanate, or a haloacetate.
 25. A scavenger supportaccording to claim 5 wherein the functionalised monomer comprisingpendant 1,3-ketoester or 1,3-ketoamide groups has the general formula 2:

wherein each X is independently 0 or NR²; R¹ and R² are as definedherein before above; R³ is H or an optionally substituted hydrocarbyl,perhalogenated hydrocarbyl or heterocyclyl group; and L is a linkinggroup.
 26. A scavenger support according to claim 3 wherein the aminofunctionalised polymer is an amino polystyrene.
 27. A scavenger supportaccording to claim 5 wherein: (a) said substituted styrenes are selectedfrom the group consisting of α-methyl styrene, methyl styrene, t-butylstyrene, bromo styrene and acetoxy styrene; and/or (b) said alkyl estersof mono-olenifically unsaturated dicarboxylic acids are selected fromthe group consisting of di-n-butyl maleate and di-n-butyl fumarate;and/or (c) said vinyl esters of carboxylic acids are selected from thegroup consisting of vinyl acetate, vinyl propionate, vinyl laurate andvinyl esters of versatic acid; and/or (d) said acrylamides are selectedfrom the group consisting of methyl acrylamide and ethyl acrylamide;and/or (e) said nitrile monomers are selected from the group consistingof acrylonitrile and methacrylonitrile; and/or (f) said esters ofacrylic acid and methacrylic acid are selected from the group consistingof methyl acrylate, ethyl acrylate, n-butyl acrylate, 2-ethylhexylacrylate, i-propyl acrylate, n-propyl acrylate, methyl methacrylate,ethyl methacrylate, n-butyl methacrylate, 2-ethylhexyl methacrylate,i-propyl methacrylate, n-propyl methacrylate, hydroxyethyl acrylate,hydroxyethyl methacrylate, N,N-dimethylaminoethyl acrylate andN,N-dimethylaminoethyl methacrylate; and/or (g) said multifunctionalacrylates and methacrylates are selected from the group consisting ofethylene glycol diacrylate, ethylene glycol dimethacrylate,trimethylolpropane triacrylate, trimethylolpropane trimethacrylate,ethylene bisacrylamide, pentaerythritol triacrylate, pentaerythritoltrimethacrylate, pentaerythritol tetraacrylate, pentaerythritoltetramethacrylate and N,N-bis-acryloyl ethylene diamine.